DESCRIPTION: (Applicant's Abstract) Since exogenous and endogenous opioids are known to modulate immune function and opiate abuse is a major etiologic factor in human AIDS, there is reason to suspect that opiates themselves affect progression of AIDS. Evidence defining the role of opiates in progression of AIDS is less than clear, however, since there are various reasonable data to support any of three possible outcomes relative to opiate effects on AIDS progression. That is, no effects, exacerbatory effects, and protective effects. Data from our laboratory, using the best model of human AIDS, a monkey model, have, in fact, shown the potential of opiates to protect as well as exacerbate progression of AIDS. The most provocative aspect of these data was that none (0/6) of our SIV-infected opiate-dependent monkeys died over a 2-yr course of study, even though the expected death rate from AIDS was near to 1 in 2. Countering these seeming protective effects, however, was evidence that withdrawal of opiates, precipitated by naloxone, caused apparent SIV induction and prominent immune disturbance, that could be regarded as exacerbatory forces in the progression of AIDS. We also found that 2/6 monkeys developed iatrogenically induced opportunistic bacterial dermatitis near the end of this study, at the site of repeated opiate injections. These findings led us to hypothesize that the effects of opiates on progression of AIDS are conditionally dependent on the stability of opiate dependency, virulence of the AIDS virus, and the nature of secondary opportunistic infections. Unfortunately, the fact that this monkey study was only a pilot study meant that firm conclusions from these findings are unwarranted. The present proposal, therefore, is aimed at validating the main findings of our previous pilot study: protection against AIDS progression, induction of SIV upon opiate withdrawal; and, potential depression of anti-bacterial phagocytic capacity. This task is to be done in a statistically meaningful way that will not compromise animal welfare. These studies should improve understanding of the role of opiates in AIDS.